This STTR application proposes development of MedicaSafe, Inc.'s Multimodal Analgesic Protection System (MAPSafe). Built around MedicaSafe's proprietary Medication Therapy Optimization (MTO) technology, MAPSafe will be designed to mitigate the myriad risks associated with prescription opioid use postoperatively and throughout recovery after surgery. Although prescription opioids are a mainstay of acute and chronic pain management, their use is associated with numerous risks. The misuse and abuse of prescription opioids has become a widespread public health problem in the United States, and iatrogenic exposure to opioids postoperatively may lead to persistent opioid use. In collaboration with Stanford University, MedicaSafe's Multimodal Analgesic Protection System (MAPSafe) will be designed to mitigate opioid misuse and abuse, delayed opioid cessation, and the subsequent development of chronic opioid use. The Analgesic Regimen Control (ARC) device represents the foundational technology for the complete MAPSafe program. An informationmotivationbehavioral skills (IMB) model will serve as the theoretical foundation for development of all MAPSafe clinical content components, which will include a Phase I Smart Tapering Module, OpioidInduced Constipation Module, and Safe Disposal Module. Phase I will involve empirical development and feasibility testing of the MAPSafe service. Activities with patients and experts in pain management will include Joint Application Development (JAD) panels to determine feasible components of the final system, including the ARC device and related clinical content; a randomized comparative pilot study to to compare performance of the MAPSafe program to treatmentasusual (TAU) in a realworld clinical environment at Stanford University, and Phase II development activities, including development of a larger randomized controlled trial (RCT) protocol testing the MAPSafe program at Stanford University, and overcoming regulatory hurdles including obtaining a special Drug Enforcement Administration (DEA) license to conduct the proposed Phase II trial.